39 <i>In vivo</i> assessment of pulmonary toxicity and oxidative stress–driven inflammation induced by brake wear particles

Abstract Particulate matter (PM) is a major contributor to air pollution and is classified into exhaust and non-exhaust sources. While exhaust PM has been effectively regulated, non-exhaust PM, such as brake wear particles (BWPs), has emerged as an important yet understudied health concern. Following the enforcement of Euro 6 emission standards, the transition toward electric vehicles with heavy battery systems has accelerated, potentially increasing brake-related emissions. Despite their environmental relevance, the inhalation toxicity of BWPs remains poorly understood. In this study, an in vivo evaluation of pulmonary toxicity was performed to investigate the acute effects of two representative BWPs—non-asbestos organic (NAO) and low-metallic (LM)—in mice. The particles were administered via pharyngeal aspiration, and bronchoalveolar lavage fluid (BALF) and histopathological analyses were performed at 1 and 7 d after exposure. Both NAO and LM particles induced dose-dependent neutrophilic inflammation, with increased total cells, neutrophils, lactate dehydrogenase (LDH) activity, and total protein levels in BALF. On a surface area dose basis, their inflammatory potency exceeded that of diesel exhaust particles (DEP; SRM 2975). NAO particles elicited stronger inflammatory and cytotoxic responses than LM, consistent with their higher intrinsic reactive oxygen species (ROS) generation. Furthermore, interleukin-1β (IL-1β) levels in BALF were positively correlated with neutrophil infiltration. These findings provide in vivo evidence that BWPs can induce acute pulmonary inflammation through oxidative stress-related mechanisms and underscore the need for regulatory attention to non-exhaust PM sources to mitigate potential human health risks.